There are numerous approaches known in the art to enhance mood and cognitive performance in normal individuals, including pharmaceutical interventions, aerobic exercise and certain cognitive training programs. Recently, certain nutraceutical agents, such as Ginkgo Biloba, and multi-agent compounds have claimed cognitive enhancing effects. Many of those agents and compounds make claims based on their inclusion of one or more individual ingredients whose clinically demonstrated efficacy level(s), or minimal therapeutic threshold amount(s), are typically not achieved in the proposed multi-agent compound or have conflicting clinical trial results.
In some examples, different supplements and formulations include multiple allegedly active ingredients and are marketed as nootropics, or cognitive enhancing agents. For example, the commercially available “Focus Factor” formulation includes over 30 ingredients, while the commercially available “Brain Lightning” formulation has nearly 20 ingredients. Another example disclosed in U.S. Pat. No. 6,964,969 to McCleary lists 47 ingredients with unknown interactions. Any clinical information and cognitive enhancement was only available for individual ingredients and not the combination of so many ingredients. Also, many of those ingredients may interact with one another in a negative manner, lessening the benefits of individual components.
Other marketed formulations include multiple active ingredients with specific effects, and therefore, often suggest that the large number of multiple active ingredients will provide additive, or even synergistic beneficial effects. There have been some clinical trials on some of these formulations and some improvements seen, but results have been mixed. Indeed, the beneficial effects of selected ingredients may individually show cognitive benefits, but when combined together in a specific range may possibly be canceled out by sensory or metabolic overstimulation, while another range of components show promise of beneficial effects. For instance, overstimulation of the cholinergic neurotransmitter system is known to cause receptor desensitization and downregulation of density and may be effected by one range of selected components, but not in another range of selected components or at a specific combination.
A few isolated compounds claiming one or more cognitive effects have been subjected to well controlled (e.g., randomized, double blind, placebo controlled) clinical trials in relatively significant sample sizes (e.g., >50). There have been some clinical trials on Ginkgo Biloba extracts and Panax Ginseng extracts alone. Researchers and product developers have combined these two components in a very specific 60:100 (3:5) ratio as a composition that is manufactured and sold under the trade name “Gincosan®” by Pharmaton SA. It is a combination of the standardized Ginkgo Biloba extract (GK501) as sold by Pharmaton SA and a Panax Ginseng extract (G115) as sold by Pharmaton SA in the 60:100 (3:5) ratio, and in typical amounts ranging from about 320 mg to about 960 mg for the total combination.
The 60:100 (3:5) ratio for the Ginkgo Biloba and Panax Ginseng is very established and almost never deviated from since it is commonly used in almost all commercial applications of the combination of Ginkgo Biloba and Panax Ginseng and well understood by those skilled in the art. It seems those skilled in the art accept this specific 60:100 (3:5) ratio of Ginkgo Biloba and Panax Ginseng as “locked in stone” and should not deviate since that is considered the optimum ratio for the combination. This ratio is exclusively used by clinicians and subject to clinical trials and evaluated in published studies such as: 1) Kennedy, D., A. Scholey, and K. Wesnes, Differential, Dose Dependent Changes in Cognitive Performance Following Acute Administration of a Ginkgo Biloba/Panax Ginseng Combination to Healthy Young Volunteers; Nutritional Neuroscience, 2001, 4(5): p. 399-412; 2) Wesnes, K., et al., The Memory Enhancing Effects of a Ginkgo Biloba/Panax Ginseng Combination in Healthy Middle-Aged Volunteers. Psychopharmacology, 2000, 152(4): p. 353-361; 3) Scholey, A. B. and D. O. Kennedy, Acute, Dose-Dependent Cognitive Effects of Ginkgo Biloba, Panax Ginseng and Their Combination in Healthy Young Volunteers: Differential Interactions with Cognitive Demand, Human Psychopharmacology: Clinical and Experimental, 2002, 17(1): p. 35-44; and 4) Kennedy, D., A. Scholey, and K. Wesnes, Modulation of Cognition and Mood Following Administration of Single Doses of Ginkgo Biloba, Ginseng, and a Ginkgo/Ginseng Combination to Healthy Young Adults, Physiology and Behavior, 2002, 75(5): p. 739-752; the disclosures which are hereby incorporated by reference in their entirety.
Another example of a trial using this well-known 60:100 (3:5) ratio for the Ginkgo Biloba/Panax Ginseng composition sold as Gincosan is disclosed in U.S. Pat. No. 6,773,729 to Petrini et al., the disclosure which is hereby incorporated by reference in its entirety. This reference discloses the 60:100 (3:5) combination of Ginkgo Biloba and Panax Ginseng as Gincosan with no deviation from that ratio and claims the benefit of enhancing the cognitive performance of a healthy child or young adult by the oral administration of 200 to 1,000 mg of this composition.
In an example, 200 to 1,000 mg of this 60:100 (3:5) Ginkgo Biloba/Panax Ginseng ratio composition marketed under the tradename Gincosan are administered with the total amount of extract divided up in one to two portions a day such as two dosages, preferably in the morning and at lunch time. The results, especially with the Serial 7s testing, showed the benefits of this composition. All of these studies, however, and numerous other studies using a combination of Ginkgo Biloba and Panax Ginseng, have been predicated on using the exact ratio for the composition and formulated to deliver typically 200 to 1,000 mg of the composition, which is formulated in the 60:100 (3:5) ratio. The Ginkgo Biloba extract contains at least 20% flavone glycosides and typically 2% to 10% terpene lactones and the Panax Ginseng extract typically contains at least 3% ginsenosides. This is a very specific 60:100 (3:5) ratio that is basically “set in stone” and rarely deviated from its specific ratio. Those skilled in the art usually do not deviate from that specific ratio when using those two ingredients out of belief the ratio is the best ratio and any change in that ratio may reduce its efficacy. However, a different ratio may impact and aid to enhance other cognitive functions such as working and long-term memory support. With the mindset that the 60:100 (3:5) ratio can never be deviated from, it becomes difficult to determine if a new ratio and composition range and the addition of additional ingredients to the Ginkgo Biloba and Panax Ginseng combination is possible.